scholarly journals Bias Attributable to Composite Outcome

2020 ◽  
Author(s):  
Fredi Alexander Diaz-Quijano
Keyword(s):  
Clinical Trials ◽  
Delta Method ◽  
List Type ◽  
Composite Outcome ◽  
Critical Component ◽  
Association Measures ◽  
Composite Outcomes ◽  
Critical Components ◽  
Relevant Component ◽  
Positive Controls

AbstractBackgroundLittle guidance is available on how composite outcomes should be interpreted, especially in situations of varied direction in the association across the event subtypes. I proposed an index to evaluate the bias attributable to composite outcomes (BACO) and applied it in recently published clinical trials.MethodsI defined the BACO index as the ratio between logarithms of the association measures of both a composite outcome and its most relevant component (e.g., any-cause mortality). By using the non-linear combination of parameters, based on the delta method, I calculated the confidence intervals and performed Wald-type tests for the null hypotheses (BACO index = 1). I applied this method in systematically selected clinical trials, and in two other preselected trials which I considered “positive controls”. These last trials have been recognized as examples of primary composite outcomes that were disregarded because of inconsistency with the treatment effect on mortality.ResultsBACO index values different from one were classified according to whether the use of composite outcomes overestimated (BACO index >1), underestimated (BACO index between zero and <1), or inverted (BACO index <0) the association between exposure and prognosis. In three of 23 clinical trials and the two positive controls, the BACO indices were significantly lower than one (using p <0.005 as a preset cutoff).ConclusionBased on the BACO index testing, researchers could predefined rules to make impartial decisions about maintaining a composite outcome as the primary endpoint or to state cautions regarding its interpretation.Key MessagesDiscrepancies between the effects on composite outcomes and those on their most critical components make the interpretation of research results a challenge.An index based on the ratio of association measures can be used to evaluate the correspondence between the composite outcome and its most critical component.This index could help to preset rules to make decisions for interpretation of clinical studies.

scholarly journals Dutch Breast Cancer Trialists' Group (BOOG)

2006 ◽  
Vol 9 (S1) ◽  
pp. 61-79
Author(s):  
Keyword(s):  
Breast Cancer ◽  
Clinical Trials ◽  
Metastatic Breast Cancer ◽  
Endocrine Therapy ◽  
Metastatic Breast ◽  
Phase Iii ◽  
List Type ◽  
First Line ◽  
Open Label ◽  
Phase Iii Study

This section provides current contact details and a summary of recent or ongoing clinical trials being coordinated by Dutch breast cancer trialists' group (BOOG). Clinical trials include:An open label randomized (inter)national multicenter comparative trial of 5 years adjuvant endocrine therapy with an LHRH agonist plus an aromatase inhibitor (goserelin + anastrozole) versus five courses FE90C chemotherapy followed by the same endocrine therapy in pre- or perimenopausal patients with hormone receptor-positive primary breast cancer (PRemenopausal Optimal Management IS Endocrine therapy). BOOG 2002-01/PROMISE. ISRCTN23561723Open label, comparative, randomized, multicenter, study of trastuzumab (Herceptin) given with docetaxel (Taxotere) versus sequential single agent therapy with trastuzumab followed by docetaxel as first-line treatment for metastatic breast cancer (MBC) patients with HER2neu overexpression. BOOG 2002-02/HERTAX ISRCTN13770586Micro-metastases and Isolated tumour cells: Robust and Relevant Or Rubbish? The MIRROR study in BREAST CANCER. BOOG 2003-03/ZonMW 3214Radiation dose intensity study in breast cancer in young women: a randomized phase III trial of additional dose to the tumor bed. BOOG 2004-01/Young Boost SRCTN45066831Microarray analysis in breast cancer to Tailor Adjuvant Drugs Or Regimens, a randomized phase III study. MATADOR, BOOG 2005-02, CKTO 2004-04 ISRCTN61893718A prospective randomised, open, multicentre, phase III study to assess different Durations of Anastrozole therapy after 2–3 years Tamoxifen as Adjuvant therapy in postmenopausal women with breast cancer. 2006-01/DATAA randomized, open-label phase III study of first line chemotherapy in elderly metastatic breast cancer patients, comparing intravenous pegylated liposomal doxorubicin with oral capecitabine; and the incorporation of a complete geriatric assessment. 2006-02/OMEGABOOG participation in International studies:. BOOG 2001-01/TEAM trial. BOOG 2001-02/AMAROS (EORTC 10981/22023). BOOG 2002-04/HERA (BIG 1-01/EORTC 10011/BO16348B). BOOG 2003-02 (BIG 1-02/IBCSG 27-02). BOOG 2003-04 (GBG 29). BOOG 2004-02/TBP (GBG 26, BIG 3-05). BOOG 2005-01/CASA (IBCSG 32-05/BIG 1-05). BOOG 2005-03/MINDACT (EORTC 10041, BIG 3-04). BOOG 2006-03/SUPREMO (BIG 2-04). BOOG 2006-04/Adjuvant lapatinib study (BIG 2-06/EGF106708)

scholarly journals The European Multicentre Bronchiectasis Audit and Research Collaboration (EMBARC): experiences from a successful ERS Clinical Research Collaboration

Breathe ◽  
2017 ◽  
Vol 13 (3) ◽  
pp. 180-192 ◽  
Author(s):  
James D. Chalmers ◽  
Megan Crichton ◽  
Pieter C. Goeminne ◽  
Michael R. Loebinger ◽  
Charles Haworth ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Clinical Research ◽  
Research Collaboration ◽  
Clinical Care ◽  
Research Priorities ◽  
Chronic Obstructive ◽  
List Type ◽  
European Respiratory Society ◽  
Obstructive Pulmonary Disease ◽  
Research Education

In contrast to airway diseases like chronic obstructive pulmonary disease or asthma, and rare diseases such as cystic fibrosis, there has been little research and few clinical trials in bronchiectasis. Guidelines are primarily based on expert opinion and treatment is challenging because of the heterogeneous nature of the disease.In an effort to address decades of underinvestment in bronchiectasis research, education and clinical care, the European Multicentre Bronchiectasis Audit and Research Collaboration (EMBARC) was established in 2012 as a collaborative pan-European network to bring together bronchiectasis researchers. The European Respiratory Society officially funded EMBARC in 2013 as a Clinical Research Collaboration, providing support and infrastructure to allow the project to grow.EMBARC has now established an international bronchiectasis registry that is active in more than 30 countries both within and outside Europe. Beyond the registry, the network participates in designing and facilitating clinical trials, has set international research priorities, promotes education and has participated in producing the first international bronchiectasis guidelines. This manuscript article the development, structure and achievements of EMBARC from 2012 to 2017.Educational aimsTo understand the role of Clinical Research Collaborations as the major way in which the European Respiratory Society can stimulate clinical research in different disease areasTo understand some of the key features of successful disease registriesTo review key epidemiological, clinical and translational studies of bronchiectasis contributed by the European Multicentre Bronchiectasis Audit and Research Collaboration (EMBARC) project in the past 5 yearsTo understand the key research priorities identified by EMBARC for the next 5 years

scholarly journals Radiation Therapy Oncology Group (RTOG)

2006 ◽  
Vol 9 (S1) ◽  
pp. 411-418
Author(s):  
Keyword(s):  
Clinical Trials ◽  
Radiation Therapy ◽  
Radiation Therapy Oncology Group ◽  
Phase Iii ◽  
Partial Breast Irradiation ◽  
List Type ◽  
Breast Irradiation ◽  
Oncology Group ◽  
Duct Carcinoma ◽  
Conformal Radiation Therapy

This section provides current contact details and a summary of recent or ongoing clinical trials being coordinated by Radiation therapy Oncology group (RTOG). Clinical trials include: RTOG 9804: Phase III trial of observation ± tamoxifen versus RT ± tamoxifen for good risk duct carcinoma in-situ(DCIS) of the female breast.NSABP B-39/RTOG 0413: A randomized phase III study of conventional whole breast irradiation (WBI) versus partial breast irradiation (PBI) for women with stage 0, I, or II breast cancer.A phase II trial to evaluate three dimensional conformal radiation therapy (3D-RT) confined to the region of the lumpectomy cavity for stage I and II breast carcinoma.

scholarly journals Osteopontin and iCD8α cells promote intestinal intraepithelial lymphocyte homeostasis

2019 ◽  
Author(s):  
Ali Nazmi ◽  
Michael J. Greer ◽  
Kristen L. Hoek ◽  
M. Blanca Piazuelo ◽  
Joern-Hendrik Weitkamp ◽  
...  
Keyword(s):  
Immune Responses ◽  
Intestinal Inflammation ◽  
Intraepithelial Lymphocytes ◽  
Intestinal Lumen ◽  
Anatomical Location ◽  
List Type ◽  
Intestinal Intraepithelial Lymphocyte ◽  
Critical Components ◽  
Cellular Immune

AbstractIntestinal intraepithelial lymphocytes (IEL) comprise a diverse population of cells residing in the epithelium at the interface between the intestinal lumen and the sterile environment of the lamina propria. Because of this anatomical location, IEL are considered critical components of intestinal immune responses. Indeed, IEL are involved in many different immunological processes ranging from pathogen control to tissue stability. However, despite their critical importance in mucosal immune responses, very little is known about the homeostasis of different IEL subpopulations. The phosphoprotein osteopontin is important for critical physiological processes, including cellular immune responses such as survival of Th17 cells and homeostasis of NK cells, among others. Because of its impact in the immune system, we investigated the role of osteopontin in the homeostasis of IEL. Here, we report that mice deficient in the expression of osteopontin exhibit reduced numbers of the IEL subpopulations TCRγδ+, TCRβ+CD4+, TCRβ+CD4+CD8α+and TCRβ+CD8αα+cells in comparison to wild-type mice. For some IEL subpopulations the decrease in cells numbers could be attributed to apoptosis and reduced cell division. Moreover, we showin vitrothat exogenous osteopontin stimulates the survival of murine IEL subpopulations and unfractionated IEL derived from human intestines, an effect mediated by CD44, a known osteopontin receptor. We also show that iCD8α IEL, but not TCRγδ+IEL, TCRβ+IEL or intestinal epithelial cells, can promote survival of different IEL populations via osteopontin, indicating an important role for iCD8α cells in the homeostasis of IEL.Key PointsOsteopontin promotes homeostasis of mouse and human IEL, mediated by its ligand CD44iCD8α cells produce osteopontin which impacts the survival of other IELLack of osteopontin renders mice susceptible to intestinal inflammation

scholarly journals Association of Breast Surgeons at the British Association of Surgical Oncology (ABS AT BASO)

2006 ◽  
Vol 9 (S1) ◽  
pp. 28-33
Author(s):  
Keyword(s):  
Clinical Trials ◽  
Ductal Carcinoma ◽  
Randomised Trial ◽  
Surgical Oncology ◽  
British Association ◽  
List Type ◽  
Current Contact ◽  
Trial Testing ◽  
Er Positive

This section provides current contact details and a summary of recent or ongoing clinical trials being coordinated by Association of Breast Surgeons at the British Association of Surgical Oncology (ABS at BASO). Clinical trials include: BASO DCIS II TRIAL: Randomised trial testing observation (no radiotherapy) against radiotherapy in women with low-risk completely excised ER positive ductal carcinoma in situ (DCIS) of the breast on adjuvant endocrine therapy.Neoadjuvant trial of preoperative exemestane or letrozole ± celecoxib in the treatment of ER positive postmenopausal early breast cancer.

Composite outcomes in clinical trials: what are they and when should they be used?

Transfusion ◽  
2010 ◽  
Vol 51 (1) ◽  
pp. 11-13 ◽  
Author(s):  
Nancy M. Heddle ◽  
Richard J. Cook
Keyword(s):  
Clinical Trials ◽  
Composite Outcomes

scholarly journals Use of multidimensional composite scores in rheumatology: parsimony versus subtlety

2020 ◽  
pp. annrheumdis-2020-216999
Author(s):  
Robert B M Landewé ◽  
Désirée van der Heijde
Keyword(s):  
Clinical Trials ◽  
Inflammatory Process ◽  
Musculoskeletal Diseases ◽  
Personalised Medicine ◽  
Disease Assessment ◽  
Treat To Target ◽  
Diverse Group ◽  
Composite Outcome ◽  
Composite Scores ◽  
Over Time

Rheumatic and musculoskeletal diseases (RMDs) form a diverse group of diseases. Proper disease assessment is pivotal, for instance to make treatment choices and for optimising outcome in general. RMDs are multidimensional diseases, entrenching many, sometimes very different aspects. Composite outcome measures (‘composites’) have become very popular to assess RMDs, because of their claim to catch all relevant dimensions of the disease into one convenient measure.In this article we discuss dimensionality of RMDs in the context of the most popular conceptual framework of RMDs, being an inflammatory process leading to some sort of damage over time. We will argue that multidimensionality not only refers to heterogeneity in disease manifestations, but also to heterogeneity in possible outcomes. Unlike most unidimensional measures, multidimensional composites may include several disease manifestations as well as several outcome dimensions into one index. We will discuss fundamental problems of multidimensional composites in light of modern strategies such as treat-to-target and personalised medicine.Finally, we will disentangle the use of multidimensional composites in clinical trials versus their use in clinical practice, and propose simple solutions in order to overcome problems of multidimensionality and to avoid harm to our patients due to overtreatment.

scholarly journals NTRK2 Fusion Driven Pediatric Glioblastoma: Identification of key molecular drivers by personalized oncology

2019 ◽  
Vol 46 (s2) ◽  
pp. S64
Author(s):  
Levine ◽  
Y Shen ◽  
K Mungall ◽  
J Serrano ◽  
M Snuderl ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Checkpoint Inhibitors ◽  
Braf V600e ◽  
Current Status ◽  
Driver Mutations ◽  
List Type ◽  
Idh1 R132h ◽  
Tyrosine Kinase 2 ◽  
Cerebellar Glioblastoma ◽  
Molecular Landscape

We describe the case of an 11-month-old girl with a rare cerebellar glioblastoma driven by a NACC2-NTRK2 (Nucleus Accumbens Associated Protein 2-Neurotrophic Receptor Tyrosine Kinase 2) fusion. Initial workup of our case demonstrated homozygous CDKN2A deletion, but immunohistochemistry for other driver mutations, including IDH1 R132H, BRAF V600E, and H3F3A K27M were negative, and ATRX was retained. Tissue was subsequently submitted for personalized oncogenomic analysis, including whole genome and whole transcriptome sequencing, which demonstrated an activating NTRK2 fusion, as well as high PD-L1 expression, which was subsequently confirmed by immunohistochemistry. Furthermore, H3 and IDH demonstrated wildtype status. These findings suggested the possibility of treatment with either NTRK- or immune checkpoint- inhibitors through active clinical trials. Ultimately, the family pursued standard treatment that involved Head Start III chemotherapy and proton radiotherapy. Notably, at most recent follow upapproximately two years from initial diagnosis, the patient is in disease remission and thriving, suggesting favorable biology despite histologic malignancy. This case illustrates the value of personalized oncogenomics, as the molecular profiling revealed two actionable changes that would not have been apparent through routine diagnostics. NTRK fusions are known oncogenic drivers in a range of cancer types, but this is the first report of a NACC2-NTRK2 fusion in a glioblastoma.LEARNING OBJECTIVESThis presentation will enable the learner to:1.Explore the current molecular landscape of pediatric high grade gliomas2.Recognize the value of personalized oncogenomic analysis, particularly in rare and/or aggressive tumors3.Discuss the current status of NTRK inhibitor clinical trials

scholarly journals Breast European Adjuvant Studies Team (BREAST)

2006 ◽  
Vol 9 (S1) ◽  
pp. 80-90
Author(s):  
Keyword(s):  
Breast Cancer ◽  
Clinical Trials ◽  
Phase Iii ◽  
List Type ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Phase Iii Trial ◽  
Adjuvant Trial ◽  
Current Contact ◽  
Positive Breast Cancer

This section provides current contact details and a summary of recent or ongoing clinical trials being coordinated by Breast European Adjuvant Studies Team (BREAST). Clinical trials include: An intergroup phase III trial to evaluate the activity of docetaxel, given either sequentially or in combination with doxorubicin, followed by CMF, in comparison to doxorubicin alone or in combination with cyclophos-phamide, followed by CMF, in the adjuvant treatment of node-positive breast cancer patients. BIG 02-98/TAX 315HERA: A randomized three-arm multi-centre comparison of 1 year and 2 years of Herceptin versus no Herceptin in women with HER2-positive primary breast cancer who have completed adjuvant chemotherapy. BIG 01-01/B016348Adjuvant trial with lapatinib and trastuzumab* (BIG) *trial title/acronym not available at time of publication.

scholarly journals Professional Vital Bleaching Using a Thin and Concentrated Peroxide Gel on Whitening Strips: An Integrated Clinical Summary

2004 ◽  
Vol 5 (1) ◽  
pp. 1-17 ◽  
Author(s):  
Robert W. Gerlach ◽  
Matthew L. Barker
Keyword(s):  
Hydrogen Peroxide ◽  
Clinical Trials ◽  
Randomized Clinical Trials ◽  
Treatment Options ◽  
New Paradigm ◽  
Tooth Color ◽  
Number Of Treatment ◽  
Advanced System ◽  
Better Than ◽  
Positive Controls

Abstract Rapid innovation in vital bleaching continues to expand the number of treatment options available to patients, particularly in the area of at-home whitening. The development of bleaching strips represented a new paradigm in the delivery of peroxide. The efficacy and safety of bleaching strip systems delivering up to 6.5% hydrogen peroxide has been established in numerous randomized clinical trials. In 2003, a novel bleaching strip with 14% hydrogen peroxide (Crest® Whitestrips® Supreme) was introduced. This advanced system carries a thinner but more concentrated gel on each strip, resulting in a relatively similar total amount of peroxide as compared to other strip systems. This 2-variable change, higher concentration gel with lowered gel volume translates to improved whitening without adversely affecting oral soft tissue tolerability and irritation. This paper provides an integrated review of 9 comparative clinical trials evaluating the whitening response (six trials) and safety (nine trials) of this novel vital bleaching system. Efficacy results for the 14% hydrogen peroxide strips were significantly (p<0.05) better than the placebo or pooled positive controls evaluated in the clinical trials assessing tooth color or shade. Adverse events were similar in type to the other vital bleaching systems. Overall, the research of 408 patients showed generally better efficacy and similar to or better tolerability for the 14% hydrogen peroxide strips compared to a selected group of marketed positive bleaching controls. Citation Gerlach RW, Barker ML. Professional Vital Bleaching Using a Thin and Concentrated Peroxide Gel on Whitening Strips: An Integrated Clinical Summary. J Contemp Dent Pract 2004 February;(5)1:001-017.

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